An “antibiotic” is broadly defined as a chemical compound that inhibits the growth of microorganism. Antibiotics can act on organisms by inhibiting cell wall synthesis, increasing cell membrane permeability, interfering with protein synthesis, or interfering with nucleic acid metabolism. In general, bacterial pathogens may be classified as either Gram-positive or Gram-negative. Antibiotic compounds with activity against both Gram-positive and Gram-negative pathogens are generally regarded as having broad spectrum activity.
When the first therapeutic antibiotic, penicillin, was introduced in the early 1940's, many believed that the threat from infectious diseases was over. However, in the past 25 years, through the abuse and misuse of antibiotics, many bacteria have developed resistance to these antibiotics. The most frequent misuse is probably in the treatment of fevers that are not caused by bacterial infections. Other common misuses and errors include choosing an ineffective antibiotic, giving inadequate or excessive doses, treating non-bacterial infections such as uncomplicated viral disease, using an improper route of administration, continuing use after bacterial resistance has developed, continuing in the presence of a serious toxic or allergic reaction, prematurely stopping therapy, using improper combinations of chemotherapeutic drugs, and relying on chemotherapy or prophylaxis to the exclusion of surgical intervention (e.g., drainage of localized infection and removal of a foreign body).
Today, there are strains of virtually every major bacterial human pathogen that are resistant to some of the most effective antibiotics. These strains include pathogens that can cause diarrhea, urinary tract infections, otitis media, meningitis, tuberculosis, gonorrhea, pneumonia, dysentery, wound infections, septicemia, bacteremia and surgical infections.
Whereas in the first decades of antibiotics discovery, development of novel antibacterial therapeutics has kept pace with the occurrence of drug-resistant bacterial strains, the widespread and sometimes indiscriminate use of antibiotics has accelerated the emergence of resistance, often against multiple drugs simultaneously and in pathogenic bacteria that cause life-threatening infections. Not only is antibiotic resistance escalating in agents of infectious diseases, but also normally nonpathogenic bacteria are acquiring resistance, and acting as opportunistic pathogens, increasingly threatening patients with weakened immune defense.
The problem of antibiotic resistance is particularly severe because examples of most antibacterial drug classes used today have been in the clinic for more than 30 years. The initial broad stream of novel antibiotics discovered from both natural and synthetic sources, has narrowed down to a trickle. Novel and potent antibiotics are required to replace the currently used drugs, which are increasingly compromised by development of resistance. Thus, there is a crucial need for novel antibacterial agents that work by novel mechanisms and effectively inhibit the growth of bacteria.